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Background Clinical trials of immune checkpoint inhibitors (ICIs) often do not include patients with advanced chronic kidney disease (CKD). We aimed to determine the safety of ICIs in patients with cancer and advanced CKD (stages 4-5 CKD, estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m2). Patients and Methods Patients with advanced CKD from the Mass General Brigham network who received ICIs (n = 91) were compared against those receiving nephrotoxic (n = 113) and non-nephrotoxic (n = 130) antineoplastic therapies, respectively. Rates of new-onset kidney failure (end-stage kidney disease or sustained eGFR ≤10 mL/minute/1.73 m2) and AKI were compared. Among ICI-treated patients, we modeled Fine-Gray subdistribution hazards to compare immune-related adverse event (irAE) risk and used Kaplan-Meier analysis to compare overall survival in patients with advanced CKD to those with eGFR ≥30 mL/minute/1.73 m2. Results Rates of new-onset kidney failure were similar at 1 year following initiation of ICIs (10.0%), nephrotoxic (6.2%), and non-nephrotoxic antineoplastic therapies (9.3%) (P = .28). AKI rates were also similar: 17.5%, 17.6%, and 20% of patients in each cohort, respectively (P = .87). Advanced CKD did not increase the risk of developing irAEs (adjusted hazard ratio [HR] 1.28, 95% CI, 0.91-1.81). However, patients with advanced CKD who received ICIs had a decreased overall survival compared with patients with eGFR ≥30 mL/minute/1.73 m2 (HR 1.30 for death, 95% CI, 1.02-1.66, P = .03). Conclusion ICIs are not associated with increased risk of AKI or new-onset kidney failure compared with other antineoplastic therapies in patients with advanced CKD. Advanced CKD did not increase the risk of extra-renal irAEs, although these patients suffered from lower overall survival.

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Background Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer; however, real-world data on kidney function among patients treated with PARPi are lacking. Methods We identified adults treated with olaparib or niraparib between 2015-2021 at a major cancer center in Boston, Massachusetts. We determined the incidence of any acute kidney injury (AKI), defined as a ≥ 1.5-fold rise in serum creatinine from baseline in the first 12 months following PARPi initiation. We calculated the percentage of patients with any AKI and sustained AKI, and adjudicated the etiologies by manual chart review. We compared trajectories in estimated glomerular filtration rate (eGFR) among PARPi-treated and carboplatin/paclitaxel-treated patients with ovarian cancer, matched by baseline eGFR. Results Of 269 patients, 60 (22.3%) developed AKI, including 43/194 (22.1%) olaparib-treated patients and 17/75 (22.7%) niraparib-treated patients. Only 9 of 269 (3.3%) had AKI attributable to the PARPi. Of the 60 patients with AKI, 21 (35%) had sustained AKI, of whom 6 had AKI attributable to the PARPi (2.2% of the whole cohort). eGFR declined within 30 days post-PARPi initiation by 9.61 ± 11.017 mL/min/1.73 m2 but recovered by 8.39 ± 14.05 mL/min/1.73 m2 within 90 days after therapy cessation. There was no difference in eGFR at 12 months post-therapy initiation in patients receiving PARPi, or controls receiving carboplatin/paclitaxel (p = .29). Conclusions AKI is common following PARPi initiation, as is a transient decline in eGFR; however, sustained AKI directly attributable to the PARPi and long-term eGFR decline are uncommon.

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ImportanceSerum creatinine–based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C–based eGFR (eGFRcys) is an alternative marker of GFR.ObjectiveTo determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr.Design, Setting, and ParticipantsThis cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date.ExposureThe primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr.Main Outcomes and MeasuresThe primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 μg/mL, (2) trimethoprim-sulfamethoxazole–related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance.ResultsA total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 μg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole–related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 μg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003).Conclusions and relevanceResults of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.

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